Update on yttrium-90-based radio-embolization for treatment of hepatocellular carcinoma

Background: Catheter-based intra-arterial therapies provided effective tumour control for unresectable hepatocellular carcinoma without distant metastasis. There was a renewed interest in the advancement of yttrium-90 radio-embolization. Method: An extensive search on the MEDLINE databases identified seven case series and two comparative studies regarding yttrium-90 radio-embolization. Results: Case series on yttrium-90 radio-embolization indicated a tumour response rate that ranged from 20% to 70%, and median survival that ranged from 7.7 to 26.6 months. Two comparative studies did not demonstrate significant difference in terms of tumour response rate and survival. One of these comparative studies demonstrated a statistically significant reduction in treatment-related neutropaenia. Conclusion: The current use of yttrium-90 radio-embolization was mainly based on small case series. Yttrium-90 radio-embolization seemed equivalent to conventional chemo-embolization in terms of tumour response rate and survival benefit. Emerging evidence suggested that yttrium-90 radio-embolization may have a more favourable side effects profile, in particular in reducing the chance of neutropaenia. Cost and logistics arrangement were two important considerations in generalizing the application of yttrium-90 radio-embolization.     

Dendritic cells cross-present latency gene products from Epstein-Barr virus-transformed B cells and expand tumor-reactive CD8(+) killer T cells

Dendritic cells (DCs) are not targets for infection by the transforming Epstein-Barr virus (EBV). To test if the adjuvant role of DCs could be harnessed against EBV latency genes by cross-presentation, DCs were allowed to process either autologous or human histocompatibility leukocyte antigen (HLA)-mismatched, transformed, B lymphocyte cell lines (LCLs) that had been subject to apoptotic or necrotic cell death. After phagocytosis of small numbers of either type of dead LCL, which lacked direct immune-stimulatory capacity, DCs could expand CD8(+) T cells capable of killing LCLs that were HLA matched to the DCs. Necrotic EBV-transformed, major histocompatibility complex (MHC) class I-negative LCLs, when presented by DCs, also could elicit responses to MHC class II-negative, EBV-transformed targets that were MHC class I matched to the DCs, confirming efficient cross-presentation of LCL antigens via MHC class I on the DC. Part of this EBV-specific CD8(+) T cell response, in both lytic and interferon gamma secretion assays, was specific for the EBV nuclear antigen (EBNA)3A and latent membrane protein (LMP)2 latency antigens that are known to be expressed at low levels in transformed cells. The induced CD8(+) T cells recognized targets at low doses, 1-10 nM, of peptide. Therefore, the capacity of DCs to cross-present antigens from dead cells extends to the expansion of high affinity T cells specific for viral latency antigens involved in cell transformation.     

Gordonia Species as Emerging Causes of Continuous-Ambulatory-Peritoneal-Dialysis-Related Peritonitis Identified by 16S rRNA and secA1 Gene Sequencing and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS)

We report here four cases of continuous ambulatory peritoneal dialysis-related peritonitis caused by three different species of Gordonia. The portal of entry was likely through Tenckhoff catheters. 16S rRNA and secA1 gene sequencing are so far the most reliable methods for the accurate identification of Gordonia species.     

Anti‐fibrotic and Anti‐tumorigenic Effects of Rhein,a Natural Anthraquinone Derivative,in Mammalian Stellate and Carcinoma Cells

Anthraquinone compounds have been recognized to possess antiinflammatory, anti‐fibrotic and anti‐tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da‐huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real‐time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC‐14), human pancreatic ductal adenocarcinoma cells (PANC‐1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha‐smooth muscle actin, type I collagen, fibronectin, N‐cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine‐threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti‐fibrotic and anti‐tumorigenic approaches. Copyright © 2014 John Wiley & Sons, Ltd.     

Biological evaluation of intervertebral disc cells in different formulations of gellan gum‐based hydrogels

Gellan gum (GG)‐based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine‐tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG‐MA) and high‐acyl gellan gums (HA‐GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA‐GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA‐GG content induced greater weight loss in the GG‐MA/HA‐GG formulation compared to GG‐MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein‐AM and ATP assays. Results showed that tunable GG‐MA/HA‐GG hydrogels were non‐cytotoxic and supported viability of rabbit NP cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are reaching epidemic levels worldwide, but data in Asia remain scarce. This cross-sectional study examined the metabolic and adipokine profiles of Chinese patients with biopsy-proven NAFLD and factors associated with severe disease. METHODS: Eighty ethnic Chinese with NAFLD and 41 healthy controls were recruited. Metabolic parameters and fasting adiponectin, tumor necrosis factor-alpha (TNF-alpha), leptin, and resistin levels were measured on the day of liver biopsy. Histology was scored according to Brunt's criteria. Metabolic syndrome was assessed by using both the International Diabetes Federation and Adult Treatment Panel III criteria. RESULTS: Twenty-eight patients had simple steatosis, and 52 patients had nonalcoholic steatohepatitis (NASH), defined as necroinflammatory grade >/=2 and/or fibrosis by Brunt's criteria. The ethnic-specific International Diabetes Federation criteria identified more cases of metabolic syndrome among NAFLD patients than the Adult Treatment Panel III criteria (70% vs 56%, P < .0001). On multivariate analysis, low adiponectin level, increased leptin level, and diabetes mellitus were associated with NAFLD. High TNF-alpha level and high body mass index were independent factors associated with NASH. TNF-alpha level had positive correlation with necroinflammatory grade (R = .35, P = .002) and fibrosis stage (R = .31, P = .005). CONCLUSIONS: Hypoadiponectinemia and elevated TNF-alpha levels are associated with the development of NAFLD and NASH, respectively, independent of other metabolic factors. Ethnic-specific definition of metabolic syndrome is more useful in the assessment of NAFLD patients.